Barrier dysfunction and pathogenesis of neutral lipid storage disease with ichthyosis (Chanarin-Dorfman syndrome)
Barrier dysfunction and pathogenesis of neutral lipid storage disease with ichthyosis (Chanarin-Dorfman syndrome)
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DOI：
10.1038/sj.jid.5700332
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发表时间：
2006-09-01
影响因子：
6.5
通讯作者：
Elias, Peter M.
中科院分区：
文献类型：
--
作者：
Demerjian, Marianne;Crumrine, Debra A.;Elias, Peter M.
鱼鳞病中性脂质沉积病（NLSDI；Chanarin-Dorfman 综合征）是一种鱼鳞病样综合征，通常与脂质水解酶 CGI-58 的突变有关。组织活检和/或血涂片中白细胞中存在油红 O 阳性、中性脂滴，加上一系列多系统异常和瘙痒性鱼鳞病样红皮病，共同诊断 NLSDI。我们调查了来自三个不相关亲属且临床诊断为 NLSDI 的患者的鱼鳞病样红皮病的发病机制。基底渗透性屏障功能和角质层（SC）完整性异常，但屏障恢复速度比正常快，如特应性皮炎。基底屏障异常与脂质微包裹体的分泌有关，首先在层状体（LB）内分离，然后在 SC 间隙内形成非层状相，由四氧化钌后固定和脂质保留树脂白色包埋相结合显示。通过胶体硝酸镧灌注，过量的水/溶质运动被限制在 SC 间隙，并进一步局限于非层状区域。过量储存脂质的相分离不仅为 NLSDI 提供了统一的致病机制，而且还为其他几种遗传性鱼鳞病样脂质代谢疾病（如隐性 X 连锁鱼鳞病和 2 型戈谢病）提供了统一的致病机制。
Neutral lipid storage disease with ichthyosis (NLSDI; Chanarin-Dorfman syndrome) is an ichthyosiform syndrome, often associated with mutations in a lipid hydrolase, CGI-58. The presence of oil red O-positive, neutral lipid droplets in tissue biopsies, and/or in leukocytes on blood smears, coupled with a constellation of multisystem abnormalities and a pruritic ichthyosiform erythroderma, are together diagnostic of NLSDI. We investigated the pathogenesis of the ichthyosiform erythroderma in patients from three unrelated kindreds with a clinical diagnosis of NLSDI. Basal permeability barrier function and stratum corneum (SC) integrity were abnormal, but barrier recovery rates were faster than normal, as in atopic dermatitis. The basal barrier abnormality was linked to the secretion of lipid micro-inclusions, first segregated within lamellar bodies (LB), which then form a non-lamellar phase within the SC interstices, shown by combined ruthenium tetroxide post-fixation and lipid-retaining resin-white embedding. With colloidal lanthanum nitrate perfusion, excess water/solute movement was restricted to the SC interstices, and further localized to non-lamellar domains. Phase separation of excess stored lipid provides a unifying pathogenic mechanism not only for NLSDI, but also in several other inherited ichthyosiform disorders of lipid metabolism, such as recessive X-linked ichthyosis and type 2 Gaucher's disease.